Platelets undergo the initial reactions which lead to hemostasis and to thrombosis. The nature of these reactions, i.e. the mechanisms whereby a specific stimulus interacts with a platelet membrane site, and those whereby the signal that a stimulation has occurred triggers an eventual platelet response are not yet fully elucidated. We seek to approach this problems by (a) isolating and characterizing the membrane binding site (i.e. receptor), utilizing photoreactive derivatives to obtain a covalently linked stimulus-receptor complex, (b) using the techniques for evaluation of changes in the platelet membrane potential and in intraplatelet pH which we have developed to prove this stimulus response, its transmembrane monovalent cation (Na ion, K ion, H ion) gradient dependence, and its metabolic requirements, using specific indicators and/or specific antagonists, (c) evaluating the role of Ca ions in these responses to stimulation, utilizing arsenazo III, a sensitive Ca ions indicator, (d) determining the effect of certain membrane perturbants as well as some drugs on the platelet and on its response to thrombin stimulation.